Toward a working definition of C3 glomerulopathy by immunofluorescence

Precise immunofluorescence criteria for C3 glomerulopathy remain to be defined. Here we tested hierarchical immunofluorescence criteria with varying stringency for C3 glomerulopathy in a cohort with dense deposit disease as the gold standard and then applied these criteria to analyze the incidence o...

Full description

Saved in:
Bibliographic Details
Published in:Kidney international 2014-02, Vol.85 (2), p.450-456
Main Authors: Hou, Jean, Markowitz, Glen S., Bomback, Andrew S., Appel, Gerald B., Herlitz, Leal C., Barry Stokes, M., D'Agati, Vivette D.
Format: Article
Language:English
Subjects:
Adult
Biomarkers - analysis
Biopsy
Complement C1q - analysis
Complement C3 - analysis
Female
Fluorescent Antibody Technique
Glomerulonephritis, Membranoproliferative - classification
Glomerulonephritis, Membranoproliferative - immunology
Glomerulonephritis, Membranoproliferative - pathology
Humans
Immunoglobulin A - analysis
Immunoglobulin G - analysis
Immunoglobulin M - analysis
Kidney Glomerulus - immunology
Kidney Glomerulus - pathology
Male
Predictive Value of Tests
Retrospective Studies
Terminology as Topic
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Precise immunofluorescence criteria for C3 glomerulopathy remain to be defined. Here we tested hierarchical immunofluorescence criteria with varying stringency for C3 glomerulopathy in a cohort with dense deposit disease as the gold standard and then applied these criteria to analyze the incidence of C3 glomerulopathy in membranoproliferative glomerulonephritis (MPGN) types 1 and 3. Among 319 archived cases of primary MPGN types 1–3, immunofluorescence reports were retrospectively coded as glomerular deposits of the following: C3 only; C3 dominant with trace or 1+ immunoglobulin (Ig)M only; and C3 dominant and at least two orders of intensity stronger than any combination of IgG, IgM, IgA, and C1q. The most restrictive criteria of ‘C3 only’ captured only half of the cases with dense deposit disease (compared with 8% of type 1 and 10% of type 3). Adding the most liberal definition identified 88% of those with dense deposit disease (compared with 31% of type 1 and 39% of type 3). The unaccounted 12% had stronger intensity of Ig staining, but it never exceeded the intensity of C3. Among MPGN type 3, 90% of C3 glomerulopathy cases were the Strife and Anders variant. Repeat biopsies in C3 glomerulopathy revealed a change in immunofluorescence pattern in 10 of 23 biopsies. The prevalence of low serum C3 and/or low C4 did not significantly differ among the three immunofluorescence criteria. Thus, ‘C3 only’ is an impractical definition of C3 glomerulopathy, and we propose a definition of C3 dominant and at least two orders of magnitude more intense than any other immune reactant, which requires validation by alternative pathway evaluation. These criteria provide a framework for identifying patients most likely to benefit from investigations of alternative complement pathway dysregulation.
ISSN:0085-2538
1523-1755
DOI:10.1038/ki.2013.340